Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom.
University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
PLoS One. 2024 Feb 2;19(2):e0297125. doi: 10.1371/journal.pone.0297125. eCollection 2024.
Pulmonary exacerbations in alpha-1 antitrypsin deficiency (AATD) related lung disease are a significant contributor to disease burden, as with usual COPD. Separating the early stages of an exacerbation from the day-to-day variation in stable COPD is central to the concerns of both clinicians and patients and has been identified as a research priority by NIHR. Clinical tools that distinguish baseline symptoms from those of an exacerbation could allow early and appropriate treatment of AECOPD to reduce the impact and potentially may slow disease progression thereby improving survival and quality of life. Candidate tools include symptom diaries and biomarkers of infection and acute inflammation. Urinary biomarkers of AECOPD have yet to be explored in AATD related COPD.
55 patients with AATD related lung disease with a history of 2 or more AECOPD in the preceding year were prospectively followed for 18 months. Each patient recorded symptom scores daily via an electronic symptom diary (eDiary) based on Bronkotest. Urinary biomarkers for AAT, NE, CRP, TIMP1 and desmosine were measured weekly using a home urinary lateral flow device. During self-reported AECOPD patients were asked to perform urine analysis on the first 7 consecutive days.
Type I Anthonisen exacerbations and episodes occurring in autumn/winter lasted longer than Type II/III exacerbations and spring/summer episodes respectively. Median urinary CRP concentration across all study participants increased during Type I AECOPD. eDiary adherence was 68% over a median of 17.8 months (IQR 15.7 to 18.5).
Use of an eDiary and urinary biomarkers to detect and characterise AECOPD remotely in AATD related lung disease is feasible over a prolonged period and paves the way for precision detection of exacerbations.
α-1 抗胰蛋白酶缺乏症（AATD）相关肺部疾病中的肺部恶化是疾病负担的重要因素，与普通 COPD 相同。将恶化的早期阶段与稳定 COPD 的日常变化区分开来是临床医生和患者关注的核心问题，并且已被 NIHR 确定为研究重点。能够区分基线症状和恶化症状的临床工具可以早期和适当治疗 AECOPD，从而减轻其影响，并可能减缓疾病进展，从而提高生存率和生活质量。候选工具包括症状日记和感染及急性炎症的生物标志物。AECOPD 的尿生物标志物在 AATD 相关 COPD 中尚未得到探索。
55 例 AATD 相关肺部疾病患者，在过去 1 年中有 2 次或以上 AECOPD 病史，前瞻性随访 18 个月。每位患者通过基于 Bronkotest 的电子症状日记（eDiary）每天记录症状评分。每周使用家用尿液横向流动设备测量 AAT、NE、CRP、TIMP1 和脱氧木糖的尿生物标志物。在自我报告的 AECOPD 期间，要求患者在连续的第 1 至 7 天进行尿液分析。
I 型 Anthonisen 恶化和秋冬季发生的发作持续时间长于 II/III 型恶化和春季/夏季发作。所有研究参与者的尿 CRP 浓度中位数在 I 型 AECOPD 期间增加。在中位数为 17.8 个月（IQR 15.7 至 18.5）的时间内，eDiary 的依从性为 68%。
在 AATD 相关肺部疾病中，长时间内使用 eDiary 和尿生物标志物远程检测和表征 AECOPD 是可行的，为精确检测恶化铺平了道路。
